Halothane, malignant hyperthermia

Malignant hyperthermia (MH) is an autosomal-dominant pharmacogenetic disorder that is triggered by exposure to inhalation of general anesthetics, such as halothane. In susceptible individuals, these drugs can induce tachycardia, a greatly increased body metabolism, muscle contracture and an elevated body temperature (above 40°C) with a rapid rate of increase. Many cases of MH are linked to a gene for type 1 ryanodine receptor (RyRl). 

Mackenzie, A.E., Allen, G., Lahey, D., Crossen, M.L., Nolan, K., Mettler, G., Worton, R.G., MacLen-nan, D.H., Korneluk, R. (1991). A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia. Anesthesiology 75,4-8. 

Ca " " release channel (ryanodine receptor) in the sarcoplasmic reticulum [mutations] (MIM 180901) Malignant hyperthermia (MIM 145600) following administration of certain anesthetics (eg, halothane)... 

The answer is e. (Kat ung, pp 428-429J Although a rare occurrence, halothane and other inhaled gas anesthetics may cause malignant hyperthermia Apparently, this occurs in genetically susceptible individuals Its onset may be accelerated by the concomitant use of succinylcholine. Immediate treatment includes administration of dantrolene. 

An area where 31P NMR spectroscopy has been widely used is in the studies on the phenomenon of malignant hyperthermia. The syndrome is initiated by halothane and therefore also referred to as halothane susceptibility, and the gene associated with the defect is named the halothane... 

The channel within the SR membrane is inhibited by a compound known as ryanodine, so that it is known as the ryanodine-sensitive Ca -channel. A mutation in the ryanodine receptor is responsible for the sensitivity, in some individuals, to the anaesthetic halothane. This sensitivity results in severe hyperthermia, a condition known as malignant hyperthermia. The explanation is that the modified receptor allows a massive Ca ion release from the SR, which is then pumped back into the SR. Thus, the rates of both release and uptake are increased, i.e. the rate of the cycle is increased so that the rate of ATP hydrolysis is very high, resulting in heat generation, and hence hyperthermia. This is analogous to an increase in rate of substrate cycles which also leads to transfer of chemical energy from ATP to heat (Chapter 2). How halothane effects the receptor cause to this release of Ca ions is not known. 

Halogenated hydrocarbon inhalation anesthetics may increase intracranial and CSF pressure. Cardiovascular effects include decreased myocardial contractility and stroke volume leading to lower arterial blood pressure. Malignant hyperthermia may occur with all inhalation anesthetics except nitrous oxide but has most commonly been seen with halothane. Especially halothane but probably also the other halogenated hydrocarbons have the potential for acute or chronic hepatic toxicity. Halothane has been almost completely replaced in modern anesthesia practice by newer agents. 

Porphyria is not the only disorder that may he inadvertently precipitated by the administration of a drug. Malignant hyperthermia is a serious, life-threatening complication of general anesthesia with halothane, methoxyflurane, and succinylcholine. It occurs in 1 in 20,000 people. Clinically, it is characterized hy high body temperature (41°C), muscle rigidity, and cardiovascular collapse. 

Larach, M. G. (1989). Standardization of the Caffeine Halothane Muscle Contracture Tst. North American Malignant Hyperthermia Group. Anesth Analg 69(4) 511-5. 

Tong, J., Oyamada, H., Demaurex, N., Grinstein, S., McCarthy, T. V., and MacLennan, D. H. (1997). Caffeine and Halothane Sensitivity of Intracellular Ca2+ Release Is Altered by 15 Calcium Release Channel (Ryanodine Receptor) Mutations Associated with Malignant Hyperthermia and/or Central Core Disease. J. Biol. Chem. 272(42) 26332-26339. 

Halothane has the highest blood/gas partition coefficient of the volatile anaesthetic agents and recovery from halothane anaesthesia is comparatively slow. It is pleasant to breathe and is second choice to sevoflurane for inhalational induction of anaesthesia. Halothane reduces cardiac output more than any of the other volatile anaesthetics. It sensitises the heart to the arrhythmic effects of catecholamines and hypercapnia arrhythmias are common, in particular atrioventricular dissociation, nodal rhythm and ventricular extrasystoles. Halothane can trigger malignant hyperthermia in those who are genetically predisposed (see p. 363). 

Allen GC, Larach MG, Kunselman AR. The sensitivity and specificity of the caffeine-halothane contracture test a report from the North American Malignant Hyperthermia Registry. The North American Malignant Hyperthermia Registry of MHAUS. Anesthesiology 1998 88(3) 579-88. 

FleweUen EH, Nelson TE. Halothane-succinylcholine induced masseter spasm indicative of malignant hyperthermia susceptibihty Anesth Analg 1984 63(7) 693-7. 

Miyamoto K, Sasaki M, Okudo T, et al. Four cases suspected of malignant hyperthermia induced by halothane and succinylchohne. Hiroshima J Anesth 1983 18 157. 

Malignant hyperthermia is a frequently fatal condition that involves severe muscle contraction and hyperthermia. Episodes are triggered by stress and/or specific volatile anesthetics, such as halothane, which cause excessive calcium release from the sarcoplasmic reticulum. The disorder is caused by a mutation in the skeletal muscle ryanodine receptor. The physiological mechanism by which stress triggers malignant hyperthermia is not fully understood. 

Acepromazine has been shown to reduce the incidence of halothane-induced malignant hyperthermia in susceptible pigs. Its protective action may result from a combination of its tranquillizing, hypothermic and/or antispasmodic effects. There are anecdotal reports that suggest that... 

Malignant hyperthermia An unusual adverse response to some inhalation anesthetics such as halothane in which there is an acute dramatic elevation in body temperature as well as tachypnea, muscle rigidity, and hyperkalemia. 

Halothane 0.8% 2.3 1 HR directly, but sensitizes heart to catecholamines Hepatitis, malignant hyperthermia, cardiac arrhythmias... 

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